Development and implementation of an Enhanced Recovery After Cranial Surgery pathway following supratentorial tumor resection at a tertiary care center.

OBJECTIVE: Controlling length of stay (LOS) reduces rates of nosocomial infections and falls, facilitates earlier return to daily activities, and decreases strain on the healthcare system. Complications following supratentorial tumor resection present early in the postoperative period, thereby enhancing the prospect of safe, early discharge. Here, the authors describe their initial experience with the development and implementation of an Enhanced Recovery After Cranial Surgery (ERACS) pathway following resection of supratentorial tumors in select patients. METHODS: This was a nonrandomized, ambispective quality improvement study of patients undergoing elective craniotomy for supratentorial tumor resection at New York University Langone Health between November 17, 2020, and May 19, 2022. Eligible patients were prospectively enrolled in either the ERACS pathway or the standard pathway. These prospective cohorts were compared to a retrospective cohort of patients who met eligibility criteria for the pathway. Patients in the ERACS pathway cohort were targeted for discharge on postoperative day 2. The primary outcome metric was hospital LOS. Secondary outcome metrics included duration of intensive care unit (ICU) care and rates of 30-day emergency department visits, readmissions, and complications. RESULTS: Over the study period, 188 of 317 patients (59.3%) who underwent supratentorial tumor resection met inclusion criteria for ERACS pathway enrollment. Sixty-three patients were enrolled in the ERACS pathway, and 125 patients completed the standard pathway. The historical cohort consisted of 332 patients who would have been eligible for ERACS enrollment. Patients in the ERACS pathway cohort had a median LOS of 1.93 days compared with 2.92 and 2.88 days for patients in the standard pathway and historical cohort, respectively (p < 0.001). There was a significant reduction in ICU utilization in ERACS pathway patients (16.0 ± 6.53 vs 29.5 ± 53.0 vs 21.8 ± 18.2 hours, p = 0.005). There were no differences in the rates of 30-day emergency department visits (12.7% vs 9.6% vs 10.9%, p = 0.809) and readmissions (4.8% vs 4.0% vs 7.8%, p = 0.279) between groups. CONCLUSIONS: Patients in the ERACS pathway cohort experienced reduced LOS and ICU utilization, with similar rates of adverse outcomes compared to standard pathway patients. The authors' initial experience suggests that an accelerated recovery pathway can be safely implemented following supratentorial tumor resection in select patients.

Subthalamic Gamma Knife Radiosurgery in Parkinson's Disease: A Cautionary Tale.

INTRODUCTION: Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has been shown to reliably improve several symptoms of Parkinson's disease (PD) in appropriately selected patients. Various factors may preclude patients from undergoing DBS and for them, non-invasive lesion-based therapies such as focused ultrasound and Gamma Knife (GK) radiosurgery may present a safer alternative. MATERIALS AND METHODS: Based on preliminary positive reports of STN GK for PD, we conducted a prospective, open-label, single-center, pilot study in PD patients deemed potential candidates for unilateral DBS based on their disease characteristics, but contraindicated due to age >74, an irreversible bleeding diathesis, or significant comorbid medical disease. Stereotactic MRI-guided GK radiosurgery was performed using a single 110- or 120-Gy dose targeting the STN contralateral to the more symptomatic extremity. Clinical follow-up and imaging assessed the safety and efficacy of the procedure over a 12-month period. RESULTS: Four PD patients with medication-refractory tremors and disabling dyskinesias underwent unilateral STN GK radiosurgery. Contraindications to DBS included high-risk comorbid cardiovas-cular disease in 3 patients and an irreversible bleeding diathesis in 1. There were no immediate post-procedural adverse events. One patient who underwent left STN GK radiosurgery developed right hemiparesis and dysarthria 7 months post-procedure followed by hospitalization at 9 months for bacterial endocarditis and liver failure from which he died. The remaining 3 patients were free of adverse events up to 12 months post-procedure and experienced a reduction in contralateral rigidity, bradykinesia, and tremor. Upon extended follow-up, 2 patients developed subacute worsening of gait. One died at 16 months due to complications of a fall whereas the other saw no change in gait up to 42 months post-procedure. All 3 patients with adverse events demonstrated a hyper-response in the targeted area on follow-up neuroimaging. DISCUSSION/CONCLUSION: Despite the potential for clinical improvement, our results suggest that unilateral STN GK radiosurgery should be approached cautiously in medically frail PD patients who may be at higher risk of GK hyper-response and neurologic complications.

Discontinuation of Postoperative Prophylactic Antibiotics After Noninstrumented Spinal Surgery: Results of a Quality Improvement Project.

BACKGROUND: Numerous medical society guidelines recommend discontinuation of antibiotics at a maximum of 24 hours after noninstrumented spinal surgery, even when a drain is left in place. As a result of these recommendations, our institution's Neurosurgery Quality Improvement Committee decided to stop administering prolonged prophylactic systemic antibiotics (PPSAs) to patients with drains after noninstrumented spinal surgery. METHODS: We retrospectively reviewed data for patients who had noninstrumented spinal surgery performed by a neurosurgeon at our institution between December 2012 and July 2014 (PPSA period) and December 2014 and July 2016 (non-PPSA period) and had a drain left in place postoperatively. In the PPSA period, patients received antibiotics until drain removal. In the non-PPSA period, patients received antibiotics for a maximum of 24 hours. RESULTS: We identified 58 patients in the PPSA period and 55 in the non-PPSA period. Discontinuation of PPSAs resulted in a nonsignificant increase in the frequency of surgical site infections (SSIs; 0% in the PPSA period vs 4% in the non-PPSA period; P = .24). CONCLUSION: After discontinuing PPSAs for patients with noninstrumented spinal procedures, as is recommended for quality improvement, we saw a nonsignificant increase in our rate of SSIs. Further monitoring of this population is warranted.

Betweenness centrality of intracranial electroencephalography networks and surgical epilepsy outcome.

OBJECTIVE: We sought to determine whether the presence or surgical removal of certain nodes in a connectivity network constructed from intracranial electroencephalography recordings determines postoperative seizure freedom in surgical epilepsy patients. METHODS: We analyzed connectivity networks constructed from peri-ictal intracranial electroencephalography of surgical epilepsy patients before a tailored resection. Thirty-six patients and 123 seizures were analyzed. Their Engel class postsurgical seizure outcome was determined at least one year after surgery. Betweenness centrality, a measure of a node's importance as a hub in the network, was used to compare nodes. RESULTS: The presence of larger quantities of high-betweenness nodes in interictal and postictal networks was associated with failure to achieve seizure freedom from the surgery (p < 0.001), as was resection of high-betweenness nodes in three successive frequency groups in mid-seizure networks (p < 0.001). CONCLUSIONS: Betweenness centrality is a biomarker for postsurgical seizure outcomes. The presence of high-betweenness nodes in interictal and postictal networks can predict patient outcome independent of resection. Additionally, since their resection is associated with worse seizure outcomes, the mid-seizure network high-betweenness centrality nodes may represent hubs in self-regulatory networks that inhibit or help terminate seizures. SIGNIFICANCE: This is the first study to identify network nodes that are possibly protective in epilepsy.

Preserved Cochlear CISS Signal is a Predictor for Hearing Preservation in Patients Treated for Vestibular Schwannoma With Stereotactic Radiosurgery.

BACKGROUND: Hearing preservation is a goal for many patients with vestibular schwannoma. We examined pretreatment magnetic resonance imaging (MRI) and posttreatment hearing outcome after stereotactic radiosurgery. METHODS: From 2004 to 2014, a cohort of 125 consecutive patients with vestibular schwannoma (VS) treated via stereotactic radiosurgery (SRS) were retrospectively reviewed. MRIs containing three-dimensional constructive interference in steady state or equivalent within 1 year before treatment were classified by two radiologists for pretreatment characteristics. "Good" hearing was defined as American Academy of Otolaryngology-Head and Neck Surgery class A. Poor hearing outcome was defined as loss of good pretreatment hearing after stereotactic radiosurgery. RESULTS: Sixty-one patients met criteria for inclusion. Most had tumors in the distal internal auditory canal (55%), separated from the brainstem (63%), oval shape (64%) without cysts (86%), and median volume of 0.85 ±â€Š0.55 cm. Pretreatment audiograms were performed a median of 108 ±â€Š173 days before stereotactic radiosurgery; 38% had good pretreatment hearing. Smaller tumor volume (p < 0.005) was the only variable associated with good pretreatment hearing. 49 (80%) patients had posttreatment audiometry, with median follow-up of 197 ±â€Š247 days. Asymmetrically decreased pretreatment cochlear CISS signal on the side of the VS was the only variable associated with poor hearing outcome (p = 0.001). Inter-rater agreement on cochlear three-dimensional constructive interference in steady state preservation was 91%. CONCLUSIONS: Decreased cochlear CISS signal may indicate a tumor's association with the cochlear neurovascular bundle, influencing endolymph protein concentration and creating an inability to preserve hearing. This important MRI characteristic can influence planning, counseling, and patient selection for vestibular schwannoma treatment.

Protracted and asynchronous accumulation of PSD95-family MAGUKs during maturation of nascent dendritic spines.

The formation and stabilization of new dendritic spines is a key component of the experience-dependent neural circuit plasticity that supports learning, but the molecular maturation of nascent spines remains largely unexplored. The PSD95-family of membrane-associated guanylate kinases (PSD-MAGUKs), most notably PSD95, has a demonstrated role in promoting spine stability. However, nascent spines contain low levels of PSD95, suggesting that other members of the PSD-MAGUK family might act to stabilize nascent spines in the early stages of spiny synapse formation. Here, we used GFP-fusion constructs to quantitatively define the molecular composition of new spines, focusing on the PSD-MAGUK family. We found that PSD95 levels in new spines were as low as those previously associated with rapid subsequent spine elimination, and new spines did not achieve mature levels of PSD95 until between 12 and 20 h following new spine identification. Surprisingly, we found that the PSD-MAGUKs PSD93, SAP97, and SAP102 were also substantially less enriched in new spines. However, they accumulated in new spines more quickly than PSD95: SAP102 enriched to mature levels within 3 h, SAP97 and PSD93 enriched gradually over the course of 6 h. Intriguingly, when we restricted our analysis to only those new spines that persisted, SAP97 was the only PSD-MAGUK already present at mature levels in persistent new spines when first identified. Our findings uncover a key structural difference between nascent and mature spines, and suggest a mechanism for the stabilization of nascent spines through the sequential arrival of PSD-MAGUKs. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1161-1174, 2017.

The Value of Diagnostic Bilateral Intracranial Electroencephalography in Treatment-Resistant Focal Epilepsy.

OBJECTIVES: We assessed the efficacy and risks of diagnostic bilateral intracranial electroencephalography (bICEEG) in patients with treatment-resistant epilepsy (TRE) with poorly lateralized epileptogenic zone on noninvasive studies as reflected by progress to resection, Engel outcome, and complication rate. METHODS: This is a retrospective chart review of 199 patients with TRE who had diagnostic bICEEG at New York University Medical Center between 1994 and 2013. Study end points were progress to resection, surgical outcome, and perioperative complications. Univariate analysis was performed with analysis of variance, t test, or Fisher exact test; multivariable analysis was performed using discriminant function analysis. RESULTS: bICEEG lateralized the epileptogenic zone and the patient had resection in 60.3% of cases. The number of depth electrodes used was positively correlated with resection, and surgical complications during bICEEG negatively correlated. Vagal nerve stimulators were implanted in 58.2% of patients who did not undergo resection and 20.7% of those who did. Among the 87 patients who progressed to resection and had more than 1-year follow-up, 47.1% were seizure free compared with 12.7% of the 55 who did not. Male sex correlated with good postoperative seizure control. The most common complication was infection requiring debridement, occurring in 3.1% of admissions (9 of 290). CONCLUSIONS: At our center, 60% of patients undergoing bICEEG progress to resection and 57% of these had more than 90% reduction in seizures. We conclude that bICEEG allows the benefits of epilepsy surgery to be extended to patients with poorly lateralized and localized TRE.

Antibiotic prophylaxis for subdural and subgaleal drains.

OBJECTIVE The authors sought to determine the effects of eliminating the use of prolonged prophylactic systemic antibiotics (PPSAs) in patients with subdural and subgaleal drains. METHODS Using a retrospective database, the authors collected data for patients over the age of 17 years who had undergone cranial surgery at their institution between December 2013 and July 2014 (PPSAs period) or between December 2014 and July 2015 (non-PPSAs period) and had subdural or subgaleal drains left in place postoperatively. RESULTS One hundred five patients in the PPSAs period and 80 in the non-PPSAs period were identified. The discontinuation of PPSAs did not result in an increase in the frequency of surgical site infection (SSI). The frequency of Clostridium difficile (CDI) and the growth of resistant bacteria were reduced in the non-PPSAs period in comparison with the PPSAs period. In the 8 months after the drain prophylaxis protocol was changed, $93,194.63 were saved in the costs of antibiotics and complications related to antibiotics. CONCLUSIONS After discontinuing PPSAs for patients with subdural or subgaleal drains at their institution, the authors did not observe an increase in the frequency of SSI. They did, however, note a decrease in the frequency of CDI and the growth of resistant organisms. It appears that not only can patients in this population do without PPSAs, but also that complications are avoided when antibiotic use is limited to 24 hours after surgery.

Loss of SynDIG1 Reduces Excitatory Synapse Maturation But Not Formation In Vivo.

Modification of the strength of excitatory synaptic connections is a fundamental mechanism by which neural circuits are refined during development and learning. Synapse Differentiation Induced Gene 1 (SynDIG1) has been shown to play a key role in regulating synaptic strength in vitro. Here, we investigated the role of SynDIG1 in vivo in mice with a disruption of the SynDIG1 gene rather than use an alternate loxP-flanked conditional mutant that we find retains a partial protein product. The gene-trap insertion with a reporter cassette mutant mice shows that the SynDIG1 promoter is active during embryogenesis in the retina with some activity in the brain, and postnatally in the mouse hippocampus, cortex, hindbrain, and spinal cord. Ultrastructural analysis of the hippocampal CA1 region shows a decrease in the average PSD length of synapses and a decrease in the number of synapses with a mature phenotype. Intriguingly, the total synapse number appears to be increased in SynDIG1 mutant mice. Electrophysiological analyses show a decrease in AMPA and NMDA receptor function in SynDIG1-deficient hippocampal neurons. Glutamate stimulation of individual dendritic spines in hippocampal slices from SynDIG1-deficient mice reveals increased short-term structural plasticity. Notably, the overall levels of PSD-95 or glutamate receptors enriched in postsynaptic biochemical fractions remain unaltered; however, activity-dependent synapse development is strongly compromised upon the loss of SynDIG1, supporting its importance for excitatory synapse maturation. Together, these data are consistent with a model in which SynDIG1 regulates the maturation of excitatory synapse structure and function in the mouse hippocampus in vivo.

Posterior Spinal Artery Aneurysm Presenting with Leukocytoclastic Vasculitis.

Rupture of isolated posterior spinal artery (PSA) aneurysms is a rare cause of subarachnoid hemorrhage (SAH) that presents unique diagnostic challenges owing to a nuanced clinical presentation. Here, we report on the diagnosis and management of the first known case of an isolated PSA aneurysm in the context of leukocytoclastic vasculitis. A 53-year-old male presented to an outside institution with acute bilateral lower extremity paralysis 9 days after admission for recurrent cellulitis. Early magnetic resonance imaging was read as negative and repeat imaging 15 days after presentation revealed SAH and a compressive spinal subdural hematoma. Angiography identified a PSA aneurysm at T9, as well as other areas suspicious for inflammatory or post-hemorrhagic reactive changes. The patient underwent a multilevel laminectomy for clot evacuation and aneurysm resection to prevent future hemorrhage and to establish a diagnosis. The postoperative course was complicated by medical issues and led to the diagnosis of leukocytoclastic vasculitis that may have predisposed the patient to aneurysm development. Literature review reveals greater mortality for cervical lesions than thoracolumbar lesions and that the presence of meningitic symptoms portents better functional outcome than symptoms of cord compression. The outcome obtained in this case is consistent with outcomes reported in the literature.

A matched cohort comparison of clinical outcomes following microsurgical resection or stereotactic radiosurgery for patients with small- and medium-sized vestibular schwannomas.

OBJECTIVE A randomized trial that compares clinical outcomes following microsurgery (MS) or stereotactic radiosurgery (SRS) for patients with small- and medium-sized vestibular schwannomas (VSs) is impractical, but would have important implications for clinical decision making. A matched cohort analysis was conducted to evaluate clinical outcomes in patients treated with MS or SRS. METHODS The records of 399 VS patients who were cared for by 2 neurosurgeons and 1 neurotologist between 2001 and 2014 were evaluated. From this data set, 3 retrospective matched cohorts were created to compare hearing preservation (21 matched pairs), facial nerve preservation (83 matched pairs), intervention-free survival, and complication rates (85 matched pairs) between cases managed with SRS and patients managed with MS. Cases were matched for age at surgery (± 10 years) and lesion size (± 0.1 cm). To compare hearing outcomes, cases were additionally matched for preoperative Class A hearing according to the American Academy of Otolaryngology-Head and Neck Surgery guidelines. To compare facial nerve (i.e., cranial nerve [CN] VII) outcomes, cases were additionally matched for preoperative House-Brackmann (HB) score. Investigators who were not involved with patient care reviewed the clinical and imaging records. The reported outcomes were as assessed at the time of the last follow-up, unless otherwise stated. RESULTS The preservation of preoperative Class A hearing status was achieved in 14.3% of MS cases compared with 42.9% of SRS cases (OR 4.5; p < 0.05) after an average follow-up interval of 43.7 months and 30.3 months, respectively. Serviceable hearing was preserved in 42.8% of MS cases compared with 85.7% of SRS cases (OR 8.0; p < 0.01). The rates of postoperative CN VII dysfunction were low for both groups, although significantly higher in the MS group (HB III-IV 11% vs 0% for SRS; OR 21.3; p < 0.01) at a median follow-up interval of 35.7 and 19.0 months for MS and SRS, respectively. There was no difference in the need for subsequent intervention (2 MS patients and 2 SRS patients). CONCLUSIONS At this high-volume center, VS resection or radiosurgery for tumors ≤ 2.8 cm in diameter was associated with low overall morbidity. The need for subsequent intervention was the same in both groups. SRS was associated with improved hearing and facial preservation rates and reduced morbidity, but with a shorter average follow-up period. Facial function was excellent in both groups. Since patients were not randomly selected for surgery, different clinical outcomes may be of different value to individual patients. Both anticipated medical outcomes and patient goals remain the drivers of treatment decisions.

LTP-induced long-term stabilization of individual nascent dendritic spines.

Learning new tasks has been associated with increased growth and stabilization of new dendritic spines. We examined whether long-term potentiation (LTP), a key cellular mechanism thought to underlie learning, plays a role in selective stabilization of individual new spines during circuit plasticity. Using two-photon glutamate uncaging, we stimulated nascent spines on dendrites of rat hippocampal CA1 neurons with patterns that induce LTP and then monitored spine survival rates using time-lapse imaging. Remarkably, we found that LTP-inducing stimuli increased the long-term survivorship (>14 h) of individual new spines. Activity-induced new spine stabilization required NMDA receptor activation and was specific for stimuli that induced LTP. Moreover, abrogating CaMKII binding to the NMDA receptor abolished activity-induced new spine stabilization. Our findings demonstrate for the first time that, in addition to enhancing the efficacy of preexisting synapses, LTP-inducing stimuli promote the transition of nascent spines from a short-lived, transient state to a longer-lived, persistent state.

Synapse-specific and size-dependent mechanisms of spine structural plasticity accompanying synaptic weakening.

Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glutamatergic activity at individual dendritic spines leads to synapse-specific synaptic weakening and spine shrinkage on CA1 neurons in the hippocampus. We found that shrinkage of individual spines in response to low-frequency glutamate uncaging is saturable, reversible, and requires NMDA receptor activation. Notably, shrinkage of large spines additionally requires signaling through metabotropic glutamate receptors (mGluRs) and inositol 1,4,5-trisphosphate receptors (IP(3)Rs), supported by higher levels of mGluR signaling activity in large spines. Our results support a model in which signaling through both NMDA receptors and mGluRs is required to drive activity-dependent synaptic weakening and spine shrinkage at large, mature dendritic spines when neural circuits undergo experience-dependent modification.

Imaging synaptic protein dynamics using photoactivatable green fluorescent protein.

Considerable evidence has accumulated that structural changes in dendritic spines and their synapses are associated with adaptive functional changes in cortical circuits, such as during circuit refinement in young animals and in learning and memory in adults. Understanding the mechanisms of circuit plasticity requires detailed investigation of the structural dynamics of dendritic spines and how they are regulated by neural activity and sensory experience. Studying the dynamic localization of synaptic proteins in dendritic spines and how their stabilization and exchange rates influence spine structural plasticity is also important. This protocol describes imaging approaches to study synaptic protein dynamics in dendritic spines of the rodent cerebral cortex. It gives a strategy for generating photoactivatable green fluorescent protein (PA-GFP)-tagged synaptic proteins and in vitro and in vivo transfection methods for coexpression of these proteins with a spectrally separable cell-filling marker (DsRed-Express). Methods for tracking synaptic protein localization using photoactivation and time-lapse imaging of PA-GFP in spiny pyramidal neuron dendrites are given. A discussion of imaging hardware and software preferences is also included. The methods described here can be used to study the dynamic processes underlying spine synapse development during the formation and plasticity of neural circuits in the mammalian brain.